Platelet C4d is associated with acute ischemic stroke and stroke severity.
OBJECTIVE
Platelets bearing complement C4d were recently reported to be 99% specific for a diagnosis of systemic lupus erythematosus (SLE) and associated with neuropsychiatric lupus. We compared the prevalence of platelet C4d and investigated the clinical associations of platelet C4d in patients with acute ischemic stroke.


METHODS
We recruited 80 patients hospitalized for acute ischemic stroke. Stroke severity was measured by the National Institutes of Health Stroke Scale (NIH-SS). Infarct volume was determined by MRI. Platelet C4d was measured by flow cytometry.


RESULTS
Mean age was 57.9 years (range: 24.6 to 86.8 years), 58% were male, and 91% were white. Eight patients (10%) with acute ischemic stroke were platelet C4d-positive, which was significantly higher in prevalence compared to healthy controls (0%, P<0.0001) and non-SLE patients with immune/inflammatory disease (2%, P=0.004). The median NIH-SS score and infarct volume for acute stroke patients were 6 (interquartile range [IQR]: 2 to 13) and 3.4 cc (IQR: 1.1 to 16.6), respectively. Platelet C4d-positive patients were more likely to have a severe stroke compared to those with negative platelet C4d (NIH-SS median: 17.5 versus 5, P=0.003). Positive platelet C4d was independently associated with stroke severity (P=0.03) after controlling for age, anticardiolipin antibody (aCL) status, and total anterior circulation of stroke involvement, and also with infarct volume (P=0.005) after controlling for age, aCL status, and old stroke by MRI.


CONCLUSIONS
Platelet C4d is associated with severe acute ischemic stroke. Platelet C4d may be a biomarker as well as pathogenic clue that links cerebrovascular inflammation and thrombosis.
Mehta
Nidhi
N
University of Pittsburgh School of the Health Sciences, University of Pittsburgh, PA, USA.
Uchino
Ken
K
Fakhran
Saeed
S
Sattar
M Abdus
MA
Branstetter
Barton F
BF
Au
Karen
K
Navratil
Jeannine S
JS
Paul
Barbara
B
Lee
Melissa
M
Gallagher
Katie M
KM
Manzi
Susan
S
Ahearn
Joseph M
JM
Kao
Amy H
AH
D000208:Acute Disease; D000368:Aged; D017153:Antibodies, Anticardiolipin / Q000097:blood; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000150:complications / Q000276:immunology; D015415:Biomarkers; D001792:Blood Platelets / Q000737:chemistry*; D002545:Brain Ischemia / Q000097:blood* / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D002318:Cardiovascular Diseases / Q000097:blood / Q000276:immunology; D015897:Comorbidity; D015935:Complement C4b; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000150:complications / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D012216:Rheumatic Diseases / Q000097:blood / Q000276:immunology; D012307:Risk Factors; D012720:Severity of Illness Index; D015912:Thrombolytic Therapy
D017153:Antibodies, Anticardiolipin; D015415:Biomarkers; D005343:Fibrinolytic Agents; D010446:Peptide Fragments; D010975:Platelet Aggregation Inhibitors; D015935:Complement C4b; C032261:complement C4d